LincRNA-p21/AIF-1/CMPK2/NLRP3 pathway promoted inflammation, autophagy and apoptosis of human tubular epithelial cell induced by urate via exosomes

• Published in: Scientific reports Vol. 14; no. 1; pp. 18146 - 15
• Main Authors: Hao, Jianbing, Guo, Xinyu, Wang, Siyu, Guo, Xiaojun, Yuan, Kun, Chen, Ruihong, Hao, Lirong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-08-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/80; 692/4022; 692/420; Allograft inflammatory factor 1; Apoptosis; Apoptosis Inducing Factor - metabolism; Apoptosis-inducing factor; Autophagy; Calcium-Binding Proteins; Cell Line; Cyclin-dependent kinase inhibitor p21; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - pathology; Exosomes; Exosomes - metabolism; Female; Humanities and Social Sciences; Humans; Hyperuricemia; Hyperuricemia - metabolism; Hyperuricemia - urine; Inflammation; Inflammation - metabolism; Inflammation - pathology; Kidney Tubules - metabolism; Kidney Tubules - pathology; Long intergenic noncoding RNA-p21; Male; Microfilament Proteins; Middle Aged; Mitochondrial nucleotide phosphokinase 2; multidisciplinary; Nephropathy; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Science; Science (multidisciplinary); Signal Transduction; Urate nephropathy; Uric acid; Uric Acid - metabolism; NLRP3; Allograft inflammatory factor 1; Mitochondrial nucleotide phosphokinase 2; Long intergenic noncoding RNA-p21; Urate nephropathy
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-69323-5

Urate nephropathy, a common complication of hyperuricemia, has garnered increasing attention worldwide. However, the exact pathogenesis of this condition remains unclear. Currently, inflammation is widely accepted as the key factor in urate nephropathy. Therefore, the aim of this study was to elucidate the interaction of lincRNA-p21/AIF-1/CMPK2/NLRP3 via exosomes in urate nephropathy. This study evaluated the effect of lincRNA-p21/AIF-1/CMPK2/NLRP3 using clinical data collected from patients with urate nephropathy and human renal tubular epithelial cells (HK2) cultured with different concentrations of urate. In clinical research section, the level of lincRNA-p21/AIF-1 in exosomes of urine in patients with hyperuricemia or urate nephropathy was found to be increased, particularly in patients with urate nephropathy. In vitro study section, the level of exosomes, inflammation, autophagy, and apoptosis was increased in HK2 cells induced by urate. Additionally, the expression of lincRNA-p21, AIF-1, CMPK2, and NLRP3 was upregulated in exosomes and HK2 cells. Furthermore, manipulating the activity of lincRNA-p21, AIF-1, CMPK2, and NLRP3 through overexpression or interference vectors regulated the level of inflammation, autophagy, and apoptosis in HK2 cells. In conclusion, the pathway of lincRNA-p21/AIF-1/CMPK2/NLRP3 contributed to inflammation, autophagy, and apoptosis of human renal tubular epithelial cell induced by urate via exosomes. Additionally, the specific exosomes in urine might serve as novel biomarkers for urate nephropathy.